Hartmann F, Renner C, Jung W, Deisting C, Juwana M, Eichentopf B, Kloft M, Pfreundschuh M
Medizinische Klinik I, Universitätskliniken des Saarlandes, Homburg, Germany.
Blood. 1997 Mar 15;89(6):2042-7.
Fifteen patients with refractory Hodgkin's disease were treated in a phase I/II trial with the natural killer (NK)-cell-activating bispecific monoclonal antibody HRS-3/A9, which is directed against the Fc(gamma)-receptor III (CD16 antigen) and the Hodgkin's-associated CD30 antigen, respectively. Median counts of NK cells and of all lymphocyte subsets were considerably decreased in the patients before therapy. HRS-3/A9 was administered 4 times every 3 to 4 days, starting with 1 mg/m2. The treatment was well tolerated, and the maximum tolerated dose was not reached at 64 mg/m2, the highest dose administered because of the limited amounts of HRS-3/A9 available. Side effects were rare and consisted of fever, pain in involved lymph nodes, and a maculopapulous rash. A total of 9 patients developed human antimouse Ig antibodies, and 4 patients developed an allergic reaction after attempted retreatment. A total of 1 complete and 1 partial remission (lasting 6 and 3 months, respectively) [corrected], 3 minor responses (1 to 11+ months), and 1 mixed response were achieved. There was no clear-cut dose-side effect or dose-response correlation. Our results encourage further clinical trials with this novel immunotherapeutic approach and emphasize the necessity to reduce the immunogenicity of the murine bispecific antibodies.
在一项I/II期试验中，15例难治性霍奇金病患者接受了天然杀伤（NK）细胞激活双特异性单克隆抗体HRS-3/A9的治疗，该抗体分别针对Fc（γ）受体III（CD16抗原）和霍奇金相关的CD30抗原。治疗前患者的NK细胞以及所有淋巴细胞亚群的计数中位数均显著降低。HRS-3/A9每3至4天给药4次，起始剂量为1mg/m²。治疗耐受性良好，由于HRS-3/A9的可用量有限，最高给药剂量为64mg/m²时未达到最大耐受剂量。副作用罕见，包括发热、受累淋巴结疼痛和斑丘疹。共有9例患者产生了人抗鼠Ig抗体，4例患者在尝试再次治疗后出现过敏反应。共实现1例完全缓解和1例部分缓解（分别持续6个月和3个月）[校正后]，3例轻度反应（持续1至11 +个月），以及1例混合反应。未发现明确的剂量-副作用或剂量-反应相关性。我们的结果鼓励对这种新型免疫治疗方法进行进一步的临床试验，并强调降低鼠源性双特异性抗体免疫原性的必要性。
